The new science of happiness: Simple, research-backed ways to boost your wellbeing

The emerging field of positive psychology: Effective strategies supported by research to enhance your overall happiness.

Research has shown that our facial expressions can impact our mood and emotions. A study conducted by researchers at the University of Tennessee at Knoxville analyzed 138 studies involving over 11,000 volunteers from around the world over a 50-year period. The findings suggest that our facial expressions play a role in influencing our emotions, highlighting the connection between our minds and bodies when it comes to experiencing happiness.

Moreover, while the common saying goes that money can't buy happiness, studies have indicated that the way we spend our money can affect our happiness levels. Research suggests that investing in experiences rather than material possessions can lead to greater feelings of happiness. For instance, a study conducted by psychologists at San Francisco State University asked participants to reflect on how their recent purchases had impacted their overall well-being.

The findings not only indicated that the volunteers derived more happiness from experiences rather than material possessions, but also that this positive effect was not influenced by the amount spent or the income of the individuals making the purchases. Additionally, the researchers discovered that experiences had a lasting impact on happiness. This could be attributed to the ability to reflect on past experiences and recapture the joy felt during those moments.

Furthermore, the freedom to make choices significantly impacts our happiness. When we believe that we have control over our future, not only do we experience greater happiness, but we also perform better in our professional lives and exhibit a more positive attitude. A study conducted with Chinese teenagers revealed that maintaining a strong belief in free will and having the autonomy to make independent choices correlated with heightened feelings of happiness. The researchers even propose that therapy sessions aimed at reinforcing the belief in free will could assist individuals in actively pursuing happiness.

Our connection to nature and the availability of natural green spaces also have a significant impact on our well-being. A recent study conducted at The Korea Advanced Institute of Science and Technology revealed that individuals living in cities with greater access to green spaces reported higher levels of contentment and happiness.

To arrive at this conclusion, the researchers utilized satellite data from cities across 60 different countries to determine the extent of accessible green spaces. They then compared this data with each country's happiness index. Remarkably, the positive correlation between green spaces and happiness persisted regardless of a country's economic status. There are several potential explanations for this phenomenon, including our inherent appreciation for the beauty of natural environments, the promotion of physical and social interaction within green spaces, and the positive impact of nature on our physical health, such as reducing blood pressure and stress levels.

However, while we have a general understanding of the activities and behaviors that can enhance our happiness, scientific research also advises us to approach its pursuit mindfully. A study conducted at Rutgers Business School discovered that when we view happiness as an achievement or believe that we must actively engage in certain actions to experience happiness, it can lead to a sense of time scarcity. Consequently, this perception can undermine and diminish our overall feelings of happiness.

According to scientific research, it is possible to increase our happiness by following a few straightforward steps. However, it is important to keep in mind that happiness should not be seen as a goal to be achieved, but rather as an experience to be savored.

Information from Science Focus

A new drug lowers levels of a protein related to ‘bad’ cholesterol

 Routine blood tests in the not-too-distant future may feature a new line item: lipoprotein(a).

High levels of this fat- and cholesterol-carrying protein increase the risk of cardiovascular disease, research suggests. But there has been little anyone can do about it. How much lipoprotein(a) a person produces is largely locked in by genetics, and the level remains relatively steady throughout life. That’s in contrast to “bad” LDL — low-density lipoprotein — cholesterol, which changes depending on diet and exercise.

Because lipoprotein(a) is genetically determined, “these people who have high levels have had it since birth, and so they can get heart disease earlier,” says Erin Michos, a preventive cardiologist at Johns Hopkins University School of Medicine who was not involved with the clinical trial.

Now, a therapy that specifically targets lipoprotein(a) levels is on the horizon. In a clinical trial, the drug, which blocks the body’s ability to make the protein, reduced people’s levels of lipoprotein(a) by as much as 80 percent, researchers report in the Jan. 16 New England Journal of Medicine. The trial also found the drug to be safe.

Another clinical trial is now under way to determine whether drastically lowering levels of lipoprotein(a) in people who already have cardiovascular disease lessens their risk of heart attack and stroke (SN: 3/15/19).

Lipoprotein(a) is made up of a particle of LDL plus a protein called apolipoprotein(a). The relationship between LDL cholesterol and cardiovascular disease risk is well-established: When there is too much LDL cholesterol in the blood, it can get into the walls of arteries, stoking an inflammatory immune response that leads to thickened walls and narrowed arteries (SN: 5/3/17).

But LDL doesn’t appear to be the whole story, says cardiologist Michelle O’Donoghue of Brigham and Women’s Hospital in Boston, who was not part of the new study. “There are people who have very well-controlled LDL cholesterol levels who do go on to have heart attacks.” As a result, “there’s been a tremendous amount of interest in lipoprotein(a) and its possible role in progression of heart disease,” she says.

The LDL component is part of the reason that cardiovascular disease risk is higher with elevated levels of lipoprotein(a). But the apolipoprotein(a) component adds to the risk, says Sotirios Tsimikas, a cardiologist at the University of California, San Diego School of Medicine in La Jolla. That protein appears to provoke a stronger inflammatory reaction than LDL does, hastening plaque development in artery walls. And apolipoprotein(a) has the potential to prevent blood clots from breaking up — bad news if an artery-blocking clot forms when a plaque ruptures.

“So in a way, it’s kind of a triple hit,” Tsimikas says. “You get all the bad things from LDL, but then you get two other things that are not good for you.”

To directly target the production of lipoprotein(a), Tsimikas and colleagues tested a drug called APO(a)-LRx, developed by Ionis Pharmaceuticals in Carlsbad, Calif., in a phase II clinical trial designed to determine the effectiveness and best dose of the treatment. The drug blocks the messenger RNA that provides genetic instructions to make the protein.

The researchers tested different drug doses in 286 patients with cardiovascular disease whose levels of lipoprotein(a) were at least 60 milligrams per deciliter of blood. Epidemiological data suggest that people with lipoprotein(a) levels between 50 and 100 mg/dL have a modest increase in the risk of cardiovascular problems, Tsimikas says. Those with levels above 100 mg/dL are at high risk. It’s estimated that about 20 percent of the population has lipoprotein(a) levels above 50 mg/dL, he says.  

At the highest dose of the drug, trial participants’ lipoprotein(a) levels dropped by an average of 80 percent by the end of the experiment.

To determine if the drug is effective at reducing the risk of heart attack and stroke, a phase III clinical trial, run by Novartis Pharmaceuticals of Basel, Switzerland, has begun recruiting participants. Researchers will test the drug or a placebo over about four years in more than 7,500 people with cardiovascular disease and lipoprotein(a) levels of 70 mg/dL or higher.

If that trial is successful, further research will be needed to see if the drug also helps people with high levels of lipoprotein(a) avoid developing cardiovascular disease in the first place.

A gene editing technique shows promise for lowering LDL cholesterol

 PHILADELPHIA ­— Ten patients enrolled in the experimental drug trial, and they were the sickest of the sick. 

All had a genetic disorder that cranks up levels of LDL cholesterol in the blood. Known as “bad cholesterol,” LDL cholesterol is infamous for clogging arteries. The patients’ disorder, called heterozygous familial hypercholesterolemia, can lead to severe heart disease at an early age — and death. 

Their arteries had been bathing in high LDL cholesterol since birth. In several patients, even typical cholesterol-lowering drugs couldn’t get the levels “even remotely under control,” says Andrew Bellinger, a cardiologist and chief scientific officer at Verve Therapeutics, a Boston-based biotechnology company.

Now, his team has tried a new approach: a genetic medicine called VERVE-101 designed to turn off a cholesterol-raising gene. Using a kind of molecular pencil, the medicine erases one DNA letter and writes in another, inactivating the gene. A single genetic change. A single medication. A potential treatment that lasts a lifetime.

That’s the hope, anyway. Bellinger presented the results of a small clinical trial called heart-1 at the American Heart Association meeting in November. VERVE-101 successfully lowered LDL cholesterol, Bellinger reported. It’s the first time anyone has shown that a DNA spelling change made inside a person’s body could have such an effect. “We can achieve clinically meaningful LDL reductions with a single dose,” he said.

Now, his team has tried a new approach: a genetic medicine called VERVE-101 designed to turn off a cholesterol-raising gene. Using a kind of molecular pencil, the medicine erases one DNA letter and writes in another, inactivating the gene. A single genetic change. A single medication. A potential treatment that lasts a lifetime.

anyone has shown that a DNA spelling change made inside a person’s body could have such an effect. “We can achieve clinically meaningful LDL reductions with a single dose,” he said.

People with familial hypercholesterolemia have lifelong symptoms, so “this whole concept of ‘one and done’ is really amazing,” says Pam Taub, a cardiologist at the University of California, San Diego who was not involved with the trial. These patients must take medications their entire lives. An infused drug like VERVE-101 — designed to alter a person’s DNA — could change treatment strategy. 

Taub points out questions about VERVE-101’s safety. One trial patient had a heart attack. Another died due to cardiac arrest. But that death was not related to treatment, Bellinger said.

Moving forward, establishing VERVE-101’s safety is crucial, agreed Karol Watson, a cardiologist at the David Geffen School of Medicine at UCLA who wasn’t involved with the new work. Editing people’s DNA to lower their cholesterol “is a strategy that could be revolutionary, but we have to make sure it’s safe,” she said at the meeting. “You are changing the genome forever.”

Here’s what we know about four key aspects of the new medicine and its history.   

VERVE-101 relies on a DNA-modifying protein called a base editor  

The composition of VERVE-101 is simple. It’s just two types of RNA molecules — molecular cousins of DNA — bundled inside a bubble of fat. 

Infused into the bloodstream, the drug travels to the liver and slips into cells. One of the RNA molecules tells cells to build a protein called an adenine base editor. The other acts as a genetic GPS, guiding the editor protein to the correct stretch of DNA

The experimental gene-editing medicine VERVE-101 packages two kinds of RNA (red and blue, center) inside a lipid nanoparticle, shown in this illustration as dots and squiggles.

The technology is CRISPR 2.0. First generation CRISPR/Cas9 tools act like molecular scissors and can disrupt genes by snipping through DNA’s strands (SN: 8/14/19). Base editors are more like molecular pencils. They edit DNA by performing chemistry on an individual DNA letter, or base, rewriting one for another, creating a new genetic sequence

“Base editors actually change a sequence that you choose into a different sequence of your choosing,” says Howard Hughes Medical Institute investigator David Liu, a chemist at Harvard University whose team invented the technology in 2016. In the case of VERVE-101, that sequence is inside the PCSK9 gene, which encodes instructions for manufacturing a protein that raises blood cholesterol levels. Just one edit in a precise location shuts PCSK9 down.

Editing wraps up less than a week after the infusion, and the drug breaks down rapidly, Bellinger said. Both the fat bubble, called a lipid nanoparticle, and its RNA cargo degrade, and within a few weeks, VERVE-101 vanishes from the body. “The only thing that’s left is the DNA change you made to the PCSK9 gene,” he said.

PCSK9 is a tempting target for gene-editing therapy 

PCSK9 has been a hot therapeutic target for the last decade or so, says Parag Joshi, a preventive cardiologist at UT Southwestern Medical Center in Dallas who was not part of the trial. 

Researchers knew that some people have PCSK9 mutations that switch the gene off. These people tended to have lower levels of LDL cholesterol — and drastically less heart disease, geneticist Helen Hobbs, an HHMI investigator at UT Southwestern Medical Center, and colleagues reported in 2006.

That landmark study pushed the field forward, Joshi says. Suddenly, scientists had proof that people could live healthy lives when PCSK9 was inactivated. That made it “a very attractive drug target,” Joshi says. It suggested that disabling PCSK9 would do no harm — and could even help, by lowering the risk of heart disease.  

Typically, the PCSK9 protein breaks down another protein called the LDL receptor. This re

ceptor is one of the good guys; it keeps bad cholesterol in check by snatching it from the blood and transporting it into liver cells for disposal. Without enough LDL receptors, LDL cholesterol levels in the blood ratchet up. 

Sekar Kathiresan, a cardiologist and Verve’s CEO and cofounder puts it succinctly: PCSK9 causes disease. “If you turn it off, all you get is health.”

Today, a few existing therapies target PCSK9, including injected antibodies or an RNA-based drug that shuts down production of the protein. Patients should take a daily statin pill to lower LDL cholesterol, Joshi says. But it’s often not enough. 

And though the therapies are theoretically effective for people with familial hypercholesterolemia, Kathiresan says, “very few patients are actually on these medications.”

His team thinks that’s because the current approach is just too heavy a burden — asking patients to take daily pills or intermittent injections for decades. “That model doesn’t seem to be working,” Kathiresan says. “And that’s what we’re trying to fix.” 

Early VERVE-101 clinical trial results reveal potential benefits — and risks 

Kathiresan’s team gave a single IV infusion of VERVE-101 to 10 people with heterozygous familial hypercholesterolemia, most of whom had severe heart disease. In those who received the highest drug doses tested, blood levels of LDL cholesterol dropped sharply, by 39 to 55 percent. And the drop appears long-lasting, Bellinger said. For the patient at the highest dose, LDL cholesterol levels held steady for 180 days after VERVE-101 infused into the bloodstream.

Steep reductions

In a clinical trial with 10 participants, people who received the highest doses of VERVE-101 tested (green and purple dots) saw steep reductions in the amount of LDL cholesterol in the blood.

Bellinger called the results “pretty much what we expected and planned,” given the team’s earlier results in nonhuman primates. But the new patient data, though preliminary, places the drug on the precipice of something bigger. “This opens the door for an entirely new way to treat heart disease,” Kathiresan says.  

VERVE-101’s utility will ultimately depend on its safety. During the trial, the team spotted some potential red flags. Four patients had minor reactions to the IV infusion, including headache and mild fever. But at the heart meeting, attention hummed over something more severe. A day after the infusion, one patient had a heart attack. Five weeks after the infusion, a different patient died when their heart suddenly stopped beating. 

That incident was probably caused by the patients’ underlying heart disease, Kathiresan says. That’s the conclusion reached by an independent data safety monitoring board that investigated the cases, he says. 

The heart attack, however, may have been related to the treatment, because it happened so soon after dosing, the monitoring board determined. Kathiresan notes, though, that the patient had been experiencing chest pains prior to the study, something they didn’t mention to the study’s investigators.

These are “very, very sick patients,” says UCSD cardiologist Taub. For future trials with the drug, she thinks such patients should be excluded.

Kathiresan’s team is now planning to enroll patients with less-advanced disease. They’re also going to check for blockages in patients’ arteries, to try and avoid including people at extremely high risk of heart attack.

In 2024, the company plans to enroll more patients at the two highest doses to determine which dose to move forward. The researchers are also testing a second version of the drug, VERVE-102, which uses a different lipid nanoparticle. Depending on those results, Verve plans to move one of the drugs on to a larger clinical trial in 2025. And if successful in people with familial hypercholesterolemia, the company intends to expand to an even broader group of patients, including those without the genetic disorder.

Developing new medicines is a long road, Kathiresan says. It can take more than a decade for a drug to go from a concept to a medication that doctors can prescribe, he says. Verve started its PCSK9-editing project in 2018. Kathiresan says he hopes to have an approved medication by the end of the decade. 

VERVE-101 is one of several base editing drugs currently in clinical trials

One potential side effect of gene-editing therapies is unintentional tweaks to DNA. VERVE-101 targets PCSK9, but what if it strays to a different spot in the genome, asks Anne Goldberg, an endocrinologist at Washington University School of Medicine in St. Louis. The technology “looks really interesting,” she says, “but we need more data.”

A DNA change at the wrong spot could put people at risk of developing cancer. With VERVE-101, Bellinger said, “we think that risk is very low.” Most of the company’s work, he said, goes into demonstrating that “we do not make edits elsewhere in the genome.” 

Today’s base editors — including the one in VERVE-101 — are much improved since the early days of the technology, says Harvard’s Liu, who was not involved with the trial. They “have very high on-target editing efficiency while also having minimal off-target editing.” 

Currently, five other base-editing clinical trials targeting other diseases, like sickle-cell disease and leukemia, are ongoing. Liu is hopeful that the gene-editing agents will give patients “a completely new lease on life.” 

Bellinger said his team thinks of VERVE-101 as a one-time procedure for health, like “molecular surgery without a scalpel.” In theory, it’s possible to reverse the edit made by VERVE-101, but it’s not what he and his colleagues envision. 

For cardiologist Donald Lloyd-Jones, who was not involved with the trial, the dream is to offer people with familial hypercholesterolemia a treatment that doesn’t rely on taking a statin pill every single day. A therapy like VERVE-101 “might be something they really consider as an option,” said Lloyd-Jones,

Currently, five other base-editing clinical trials targeting other diseases, like sickle-cell disease and leukemia, are ongoing. Liu is hopeful that the gene-editing agents will give patients “a completely new lease on life.” 

Bellinger said his team thinks of VERVE-101 as a one-time procedure for health, like “molecular surgery without a scalpel.” In theory, it’s possible to reverse the edit made by VERVE-101, but it’s not what he and his colleagues envision. 

For cardiologist Donald Lloyd-Jones, who was not involved with the trial, the dream is to offer people with familial hypercholesterolemia a treatment that doesn’t rely on taking a statin pill every single day. A therapy like VERVE-101 “might be something they really consider as an option,” said Lloyd-Jones, of Northwestern University Feinberg School of Medicine in Chicago.

“If we get those safety data, if we get those efficacy data,” he said at the meeting, “I think this would be a very interesting approach to a lifetimetoday fix.”Source: Science News